1887

Abstract

Lipo-oligosaccharide (LOS) is a major surface component and virulence factor of the human respiratory pathogen . Two late acyltransferase genes, and , have been identified involved in the incorporation of acyloxyacyl-linked secondary acyl chains into lipid A during LOS biosynthesis. In this study, a double mutant with a deletion of both the and genes in strain O35E was constructed and named O35ElpxXL. Structural analysis of lipid A showed that the O35ElpxXL mutant lacked two decanoic acids (10 : 0) and one dodecanoic (lauric) acid (12 : 0). In comparison with the O35E parental strain and the single mutants O35ElpxX and O35ElpxL, the double mutant O35ElpxXL displayed prominently decreased endotoxin content, reduced resistance to normal human serum and accelerated bacterial clearance at 0, 3 and 6 h after an aerosol challenge in a mouse model of bacterial pulmonary clearance. These results indicate that these two genes encoding late acyltransferases responsible for lipid A biosynthesis jointly contribute to the biological activities and pathogenicity of The double mutant O35ElpxXL with dramatically reduced toxicity is proposed as a potential vaccine candidate against infections for further investigation.

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2013-06-01
2024-03-28
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References

  1. Caroff M., Tacken A., Szabó L. 1988; Detergent-accelerated hydrolysis of bacterial endotoxins and determination of the anomeric configuration of the glycosyl phosphate present in the “isolated lipid A” fragment of the Bordetella pertussis endotoxin. Carbohydr Res 175:273–282 [View Article][PubMed]
    [Google Scholar]
  2. Edebrink P., Jansson P. E., Rahman M. M., Widmalm G., Holme T., Rahman M., Weintraub A. 1994; Structural studies of the O-polysaccharide from the lipopolysaccharide of Moraxella (Branhamella) catarrhalis serotype A (strain ATCC 25238). Carbohydr Res 257:269–284 [View Article][PubMed]
    [Google Scholar]
  3. Forsberg L. S., Carlson R. W. 1998; The structures of the lipopolysaccharides from Rhizobium etli strains CE358 and CE359. The complete structure of the core region of R. etli lipopolysaccharides. J Biol Chem 273:2747–2757 [View Article][PubMed]
    [Google Scholar]
  4. Gao S., Peng D., Zhang W., Muszyński A., Carlson R. W., Gu X.-X. 2008; Identification of two late acyltransferase genes responsible for lipid A biosynthesis in Moraxella catarrhalis. FEBS J 275:5201–5214 [View Article][PubMed]
    [Google Scholar]
  5. Gorter A. D., Oostrik J., van der Ley P., Hiemstra P. S., Dankert J., van Alphen L. 2003; Involvement of lipooligosaccharides of Haemophilus influenzae and Neisseria meningitidis in defensin-enhanced bacterial adherence to epithelial cells. Microb Pathog 34:121–130 [View Article][PubMed]
    [Google Scholar]
  6. Gu X.-X., Chen J., Barenkamp S. J., Robbins J. B., Tsai C. M., Lim D. J., Battey J. 1998; Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine candidates for Moraxella (Branhamella) catarrhalis. Infect Immun 66:1891–1897[PubMed]
    [Google Scholar]
  7. Holme T., Rahman M., Jansson P. E., Widmalm G. 1999; The lipopolysaccharide of Moraxella catarrhalis structural relationships and antigenic properties. Eur J Biochem 265:524–529 [View Article][PubMed]
    [Google Scholar]
  8. Hu W. G., Chen J., Battey J. F., Gu X. X. 2000; Enhancement of clearance of bacteria from murine lungs by immunization with detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins. Infect Immun 68:4980–4985 [View Article][PubMed]
    [Google Scholar]
  9. Karalus R., Campagnari A. 2000; Moraxella catarrhalis: a review of an important human mucosal pathogen. Microbes Infect 2:547–559 [View Article][PubMed]
    [Google Scholar]
  10. Lugade A. A., Bogner P. N., Thanavala Y. 2011; Murine model of chronic respiratory inflammation. Adv Exp Med Biol 780:125–141 [View Article][PubMed]
    [Google Scholar]
  11. Masoud H., Perry M. B., Richards J. C. 1994; Characterization of the lipopolysaccharide of Moraxella catarrhalis. Structural analysis of the lipid A from M. catarrhalis serotype A lipopolysaccharide. Eur J Biochem 220:209–216 [View Article][PubMed]
    [Google Scholar]
  12. Murphy T. F., Brauer A. L., Grant B. J., Sethi S. 2005; Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response. Am J Respir Crit Care Med 172:195–199 [View Article][PubMed]
    [Google Scholar]
  13. Peng D., Choudhury B. P., Petralia R. S., Carlson R. W., Gu X.-X. 2005a; Roles of 3-deoxy-d-manno-2-octulosonic acid transferase from Moraxella catarrhalis in lipooligosaccharide biosynthesis and virulence. Infect Immun 73:4222–4230 [View Article][PubMed]
    [Google Scholar]
  14. Peng D., Hong W., Choudhury B. P., Carlson R. W., Gu X.-X. 2005b; Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate. Infect Immun 73:7569–7577 [View Article][PubMed]
    [Google Scholar]
  15. Song W., Ma L., Chen R., Stein D. C. 2000; Role of lipooligosaccharide in Opa-independent invasion of Neisseria gonorrhoeae into human epithelial cells. J Exp Med 191:949–960 [View Article][PubMed]
    [Google Scholar]
  16. Tsai C. M., Frasch C. E. 1982; A sensitive silver stain for detecting lipopolysaccharides in polyacrylamide gels. Anal Biochem 119:115–119 [View Article][PubMed]
    [Google Scholar]
  17. Tzeng Y. L., Datta A., Kolli V. K., Carlson R. W., Stephens D. S. 2002; Endotoxin of Neisseria meningitidis composed only of intact lipid A: inactivation of the meningococcal 3-deoxy-d-manno-octulosonic acid transferase. J Bacteriol 184:2379–2388 [View Article][PubMed]
    [Google Scholar]
  18. Vaneechoutte M., Verschraegen G., Claeys G., Van Den Abeele A. M. 1990; Serological typing of Branhamella catarrhalis strains on the basis of lipopolysaccharide antigens. J Clin Microbiol 28:182–187[PubMed]
    [Google Scholar]
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